Assessment of serum MMP-9, TIMP-1 levels and MMP-9/TIMP-1 ratio in migraine patients with and without aura

Abstract

Matrix metalloproteinases (MMP) are the enzymes responsible for proteolytic ac­tivity of extracellular matrix proteins. Tissue inhibitors of metalloproteinases (TIMPs) are their endogenous inhibitors. MMP-9 acts on the basal membrane of cerebellar epithe­lium and is antagonized by TIMP-1. MMP-9/TIMP-1 ratio exhibits the net activity of MMP-9. These enzymes are thought to have a role in migraine physio­pathogenesis. Total of 50 treatment-naive migraine patients (25 with aura and 25 without aura) with no other diseases, were included. 25 healthy control subjects of cor­responding age and gender were enrolled. For MMP-9 and TIMP-1 analysis, one serum sample from control group and two samples from patients were collected (during headache and headache-free periods). The enzyme levels were quantitatively analyzed by competitive ELISA method. Duration and severity of the pain and duration of the disease were recorded. There was no significant difference in MMP-9 levels between patient and control groups during headache and headache-free periods (p: 0,746, p: 0,243). TIMP-1 levels were significantly lower and MMP-9/TIMP ratios were higher comparing with the control group (p: 0.001). Positive correlation was obtained between the duration of pain and MMP-9 levels in the headache-free period for both patient groups (p<0.05). There was also a positive correlation between MMP-9/TIMP-1 ratio and severity of pain (p<0.05). In our study, low TIMP-1 levels of patients in both headache and headache-free periods suggest that disturbance of proteolytic protection has a role in neuro-inflammation and pain in migraine. Therefore, these enzymes could be potential targets in migraine therapies.

Biomarkers of Migraine: An Integrated Evaluation of Preclinical and Clinical Findings

“…Following this hypothesis, the plasma levels of MMP-9 are reported to be significantly higher in EM than in HC in the interictal period and even higher during the headache phase [ 173 , 174 , 175 ]. These findings, however, were not confirmed by other researchers, who found no changes in MMP-9 levels between subjects with migraine and HC [ 176 , 177 ], suggesting that, although increased MMP-9 levels are intriguing, a more thorough examination is necessary.…”

A role of NLRP3 and MMP9 in migraine progression: a systematic review of translational study

“…During the 12-week double-blind observation period, a single infusion of 300 mg eptinezumab significantly reduced the number of monthly migraine attack days compared to the placebo group (23)(24)(25). Nowadays, researchers are especially targeting NLRP3 inflammasomes (26)(27)(28)(29)(30) which has a robust connection to migraine and predicting MMP9 additionally playing a major role in the migraine attack (31)(32)(33).…”